title: Orally disintegrating tablet of novel salt of antiepileptic drug: formulation strategy and evaluation.
abstract: The aim of present research was to design and evaluate orally disintegrating tablet (ODT) of novel lamotrigine-cyclamate salt. Box-Behnken response surface methodology was selected to design the optimized formulation. The independent factors selected were tablet hardness (X1), disintegrant (X2) and lubricant (X3) levels, and responses chosen were disintegration time (DT, Y1), friability (Y2), T50 (Y3), and T90 (Y4). The tablets were also characterized for drug uniformity by near infrared chemical imaging (NIR-CI) and taste masking evaluation by electronic tongue. All the selected independent variables were statistically (p<0.05) effect the Y1 while Y2, Y3, and Y4 affected only by X2. The optimized ODT was found to meet the regulatory requirement of DT and friability specification. The NIR-CI images indicated uniform distribution of active and inactive ingredients within the tablets. The electronic tongue results were analyzed by principle component analysis (PCA). It indicated that novel salt of lamotrigine and its ODT formulation have a taste similar to cyclamic acid which is indicated by close proximity on PCA score plot, lower Euclidean distance, and high discrimination index values. Furthermore, these parameters were very close to ODT placebo formulation. On the other hand, lamotrigine, its ODT, and placebo formulation were far from each other. In summary, lamotrigine salt provides another avenue for pediatric friendly formulation for children and will enhance patience compliance.
authors.affiliation: Division of Product Quality and Research, Center of Drug Evaluation and Research, Food and Drug Administration, MD, USA.
authors.forename: Ziyaur
authors.initials: Z
authors.lastname: Rahman
authors.forename: Akhtar
authors.initials: A
authors.lastname: Siddiqui
authors.forename: Mansoor A
authors.initials: MA
authors.lastname: Khan
mesh_terms: D000284:Administration, Oral; D000704:Analysis of Variance; D000927:Anticonvulsants / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002648:Child; D003494:Cyclamates / Q000737:chemistry; D005079:Excipients / Q000737:chemistry; D006244:Hardness; D006801:Humans; D000077213:Lamotrigine; D010919:Placebos; D025341:Principal Component Analysis; D012492:Salts / Q000737:chemistry; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D019265:Spectroscopy, Near-Infrared; D013499:Surface Properties; D013607:Tablets; D013649:Taste; D014227:Triazines / Q000737:chemistry
chemical_list: D000927:Anticonvulsants; D003494:Cyclamates; D005079:Excipients; D010919:Placebos; D012492:Salts; D013607:Tablets; D014227:Triazines; D000077213:Lamotrigine
keywords: Disintegration time; Dissolution; Electronic tongue; Lamotrigine-cyclamate salt; Near infrared chemical imaging; Orally disintegrating tablet